The experiments described in this proposal are aimed at the analysis of a newly cloned gene, SMR3. Spontaneous alterations at this locus confer multiple drug resistance in yeast. Genetic analysis of this locus is particularly important for several reasons. First, such a study may help us understand the phenomenon of multidrug resistance in clinically significant, but genetically cumbersome organisms such as Candida, Plasmodium and humans. Secondly, the yeast locus is structurally intriguing. Mutations of drug resistance are unstable. Furthermore, SMR3 appears to be a member of a complex multi-locus region that mediates drug resistance. By using classical genetics, nucleic acid hybridization techniques and DNA sequencing, we should learn whether this gene is analogous to the tumor counterpart as well as the basis of the observed instability.